Enhanced choline metabolism in a rodent rhabdomyosarcoma model: correlation between RT-PCR and translational 3 T H-MRS

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• 作者：Denis Rommel ; Jorge Abarca-Quinones ; Christine De Saeger ; Frank Peeters ; Isabelle Leclercq ; Thierry Duprez
• 关键词：Animal model ; Cancer imaging ; Choline ; Gene expression ; H-MRS ; RT-PCR
• 刊名：Magnetic Resonance Imaging
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：30
• 期：7
• 页码：1010-1016
• 全文大小：425 K

文摘

Purpose

To investigate which transmembrane choline transporters and intracellular choline kinases play a prominent role at gene expression level in the rise of the total choline (tCho) peak at proton MR spectra in a rodent rhabdomyosarcoma model.

Materials and Methods

Twenty-two rats bearing grafted bilateral syngenic rhabdomyosarcoma were examined on a clinical 3 T MR system. Total choline concentration was measured from proton MR spectra using cubic centimeter volumes of interest (VOIs) located contiguously along the greater axis of the tumour. After euthanasia, cubic centimetre tissue specimens corresponding to Proton magnetic resonance spectroscopy (H-MRS) VOIs were frozen in liquid nitrogen. Out of 89 H-MRS voxels, only 39 with a corresponding tissue specimen suitable for biochemical processing were included in the analysis. RNA was extracted from all the 39 samples and reverse-transcribed into cDNA. Choline kinase ¦Á and ¦Â gene expression as well as genes of the transmembrane transporters OCT1, OCT2, OCT3, CTL1, CTL3, CTL4 and CHT1 were studied using reverse transcriptase polymerase chain reaction. The expression level of each gene (¦¤Ct), was normalized referred to that of the RPL19 gene. The Spearman rank correlation coefficient was used to analyse variables.

Results

There was no overexpression of genes coding for kinases; however, significant correlation was observed between kinase ¦Á sub-type and the tCho peak (P=.002; r=0.51). OCT1 was the most overexpressed transporter gene. Less overexpressed CTL1 gene was significantly correlated with the tCho peak (P=.02; r=0.38).

Conclusion

Choline transporters seem to play a predominant role in the increase in total choline concentration at the gene expression level in our model.